Anti-angiogenesis Function of Ononin via Suppressing the MEK/Erk Signaling Pathway.

Abstract

Angiogenesis is a complicated pathological process and plays an important role in modulating tumor development. Flavonoids, sharing the basic functional group with estrogen, have been utilized as chemopreventive agents to inhibit endothelial cell angiogenesis and also suppress tumor cell proliferation. Ononin, also referred to as formononetin-7-O-β-d-glucoside, is one of the bioactive chemicals found within many functional food or plants. The anticancer functions of ononin have been reported both in vitro and in vivo. However, the anti-angiogenetic properties of ononin have not been reported. The possible efficacies of ononin against angiogenesis was verified in cultured endothelial cells. Ononin suppressed vascular endothelial growth factor (VEGF)-induced HUVEC migration, invasion. and tube formation activity after 48 h. The apoptosis rate and specific markers, i.e., Bax/Bc-2 ratio, cleaved caspase 3/9 (Cl-caspase 3/9), and cytochrome c (Cyto c), were enhanced in the ononin-treated group. On the other hand, the protein expressions levels of hypoxia-inducible factor 1α (HIF-1α), mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK), and vascular endothelial growth factor receptor 2 (VEGFR2) were restricted after ononin treatment for 2 days in VEGF-pretreated endothelial cells. In summary, ononin acts as a candidate for angiogenetic-related disease prevention and treatment.

• Authors: Guowei Gong, Yuzhong Zheng, Xiangpeng Kong, Zhen Wen
• Journal: Journal of natural products (J Nat Prod) Vol. 84 Issue 6 Pg. 1755-1762 (06 25 2021) ISSN: 1520-6025 [Electronic] United States
• PMID: 34029083 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Angiogenesis Inhibitors
• Glucosides
• HIF1A protein, human
• Hypoxia-Inducible Factor 1, alpha Subunit
• Isoflavones
• calycosin-7-O-beta-D-glucoside
• KDR protein, human
• Vascular Endothelial Growth Factor Receptor-2
• Mitogen-Activated Protein Kinase Kinases

Topics

• Angiogenesis Inhibitors (pharmacology)
• Glucosides (pharmacology)
• Human Umbilical Vein Endothelial Cells (drug effects)
• Humans
• Hypoxia-Inducible Factor 1, alpha Subunit
• Isoflavones (pharmacology)
• Mitogen-Activated Protein Kinase Kinases
• Neovascularization, Pathologic
• Signal Transduction (drug effects)
• Vascular Endothelial Growth Factor Receptor-2